title: Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: The effect of neoadjuvant therapy.
abstract: Epithelial cancer cells are likely to undergo epithelial-mesenchymal transition (EMT) prior to entering the peripheral circulation. By undergoing EMT, circulating tumor cells (CTCs) lose epithelial markers and may escape detection by conventional methods. Therefore, we conducted a pilot study to investigate mRNA transcripts of EMT-inducing transcription factors (TFs) in tumor cells from the peripheral blood (PB) of patients with primary breast cancer (PBC). PB mononuclear cells were isolated from 52 patients with stages I-III PBC and 30 healthy donors (HDs) and were sequentially depleted of EpCAM(+) cells and CD45(+) leukocytes, henceforth referred to as CD45(-). The expression levels of EMT-inducing TFs (TWIST1, SNAIL1, SLUG, ZEB1 and FOXC2) in the CD45(-) cells were determined using quantitative real-time polymerase chain reaction. The highest level of expression by the CD45(-) cell fraction of HD was used as "cutoff" to determine if samples from patients with PBC overexpressed any EMT-inducing TFs. In total, 15.4% of patients with PBC overexpressed at least one of the EMT-inducing TF transcripts. Overexpression of any EMT-inducing TF transcripts was more likely to be detected in patients with PBC who received neoadjuvant therapies (NAT) than patients who received no NAT (p = 0.003). Concurrently, CTCs were detected in 7 of 38 (18.4%) patients by CellSearch® and in 15 of 42 (35.7%) patients by AdnaTest™. There was no association between the presence of CTCs measured by CellSearch® or AdnaTest™. In summary, our results demonstrate that CTCs with EMT phenotype may occur in the peripheral circulation of patients with PBC and that NAT is unable to eliminate CTCs undergoing EMT.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Mego
authors.forename: Sendurai A
authors.initials: SA
authors.lastname: Mani
authors.forename: Bang-Ning
authors.initials: BN
authors.lastname: Lee
authors.forename: Changping
authors.initials: C
authors.lastname: Li
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Evans
authors.forename: Evan N
authors.initials: EN
authors.lastname: Cohen
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.forename: Summer A
authors.initials: SA
authors.lastname: Jackson
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: Anthony
authors.initials: A
authors.lastname: Lucci
authors.forename: James M
authors.initials: JM
authors.lastname: Reuben
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D020360:Neoadjuvant Therapy; D009360:Neoplastic Cells, Circulating; D009687:Nuclear Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics*; D051879:Twist-Related Protein 1 / Q000235:genetics; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C082078:mesenchyme fork head 1 protein; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human